rs242936

Variant names:

• chr17-45821843-A-G
• rs242936
• NM_004382.5:c.327+403A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-45821843-A-G
• chr17-45821843-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004382.5(CRHR1):​c.327+403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 152,292 control chromosomes in the GnomAD database, including 61,173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61173 hom., cov: 34)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 10 publications found

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

LINC02210-CRHR1 (HGNC:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.327+403A>G		intron_variant	Intron 4 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.327+403A>G		intron_variant	Intron 4 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-199+403A>G		intron_variant	Intron 6 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136284 AN: 152174 Hom.: 61131 Cov.: 34

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.894

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.896 AC: 136382 AN: 152292 Hom.: 61173 Cov.: 34 AF XY: 0.899 AC XY: 66970 AN XY: 74474

African (AFR) AF: 0.860 AC: 35729 AN: 41544

American (AMR) AF: 0.928 AC: 14208 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.971 AC: 4688 AN: 4826

European-Finnish (FIN) AF: 0.923 AC: 9798 AN: 10618

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60697 AN: 68018

Other (OTH) AF: 0.895 AC: 1893 AN: 2116

Alfa AF: 0.894 Hom.: 73026

Bravo AF: 0.895

Asia WGS AF: 0.977 AC: 3398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	9.8
DANN	Benign	0.68
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs242936; hg19: chr17-43899209;